Prior Red Light Exposure May Not Reduce Blue-Prompted Pupil Constriction

Blue light’s reputation precedes itself every time a patient asks for blue light-filtering eyeglass lenses. Previous studies have even suggested that a sprinkling of red light exposure may be helpful before bedtime. Elizabeth Day, OD, MS and Andrew Hartwick, OD, PhD, FAAO, presented an investigation at the American Academy of Optometry in Boston that explored whether pupil constriction from prior flickering long-wavelength light can impact melanopsin activation from blue light. 

Circadian rhythms are thought to be influenced by the pathway involving a light-sensitive protein, the photopigment melanopsin, contained in intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells are especially sensitive to short-wavelength light, and past research examining ipRGCs have employed bright and consistent blue light. “Obviously, the lighting in our natural environment is more complex, and so I’m interested in how these cells respond to different lighting situations,” explained Dr Hartwick, Associate Professor at Ohio State University College of Optometry. In our environment, light fluctuates and objects move.

So, ipRGC cells activate melanopsin in response to blue light, but ipRGC neurons can also be prompted by acetylcholine (ACh), a neurotransmitter which is secreted by another retinal member, starburst amacrine cells. Flickering light is effective to trigger ACh release.

In this investigation, tropicamide was administered to dilate the left eyes of 7 participants (mean age 26.7±4.3 years, 42.9% men). Flickering red light below the melanopsin threshold was shown to the left eye, and pupil constriction in the right eye was recorded. Each trial consisted of 15 minutes of dark adaptation, 2 minutes of red stimulus, 1 minute of continuous blue light above the melanopsin threshold, and 2 concluding minutes of red light. Three trials were completed with flicker frequencies of 0 Hz, 6 Hz, and 30 Hz. 

During the blue light exposure, average pupil constriction was 76.1±3.1% standard error of mean (SEM), and constriction was similar in the 3 trials. During the flickering red light 0 Hz stimulus, average pupil constriction was 45.3±6.0%. At 6 Hz flicker, pupil response was 60.9±7.1%, and during the 30 Hz stimulus, pupil constriction was 39.6±4.8%. Red light-prompted pupil constriction differences between trials approached statistical significance at (P =.057), and was most evident between 6 Hz and 30 Hz. Blue light produced significantly greater pupil constriction than red light at any flicker frequency (P <.001).

Findings agree with previous studies that show a 6 Hz flickering stimulus increases pupil constriction, demonstrating ACh-driven activation of ipRGC cells. “While prior in vitro work from our lab indicated that melanopsin-based responses were occluded during activation of ipRGC acetylcholine receptors, these results indicated that pupil constriction to bright (i.e. above melanopsin activation threshold) blue light was not significantly dampened by preceding flickering red light stimuli,” according to the report.

The data suggests there are other modes of stimulation for ipRGCs beyond sunlight. “This could explain how our pupils stay constricted under dimmer indoor artificial lighting situations, and lead to better understanding of how our circadian rhythms are affected by indoor lighting,” Dr Hartwick explained. He added, “it is likely too simple to think blue light at night is bad for sleep while red light is not.”

Reference

Day E, Hartwick A. Pupil constriction evoked by flickering red light and the effect on subsequent melanopsin-driven pupil responses. Poster presented at the American Academy of Optometry 2021 meeting; November 3-6, 2021; Boston. Board #92.